1995 …2021
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Personal profile

Biography

Helicobacter pylori (Hp) is a prototype of a cancer-inducing pathogen. This motile rod-shaped Gram negative bacterium colonises persistently in the human stomach, causing chronic gastritis and gastric cancer in susceptible individuals. Virulent Hp expresses a Type IV secretion system (T4SS), a major virulence factor which functions as macromolecular machine gun that 'shoots' virulence proteins and peptidoglycan molecules into the host cells. Recently, we discovered that a novel adhesin of Hp, CagL, is expressed on the surface of T4SS and is able to dock onto integrin receptors on human gastric epithelial cells, turn on integrins and simultaneously trigger the secretion of other virulence molecules into the stomach cells. Once intracellular, the Hp virulence factors including CagA and peptidoglycan then interact with specific host signalling molecules to trigger activation of host tyrosine kinases, nuclear factor kappa B (NFΚB) and/or downstream proinflammatory responses such as the secretion of cytokines. Meanwhile, the vacuolating toxin secreted by Hp dysregulates normal host cell functions, causes severe cytotoxicity and disrupts the gastric epithelium. The molecular basis of how Helicobacter infection progresses into cancers however remains largely a mystery. Our lab is interested in using a multi-disciplinary approach to understand the pathogenesis of Helicobacter-associated malignancies.

Keywords

  • Cancer
  • Medical microbiology
  • Helicobacter pylori
  • pathogenesis
  • Gastric cancer
  • Gastritis
  • Inflammation
  • Infection and immunity
  • Type IV secretion
  • Bacterial toxins
  • Cell signalling
  • Integrin receptors
  • Microbial oncogenesis

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Projects 2009 2021

Research Output 1995 2018

The Helicobacter pylori Methylome: Roles in Gene Regulation and Virulence

Gorrell, R. & Kwok, T., Feb 2017, Molecular Pathogenesis and Signal Transduction by Helicobacter pylori. Tegtmeyer, N. & Backert, S. (eds.). Springer, Vol. 400. p. 105-127 23 p. (Current Topics in Microbiology and Immunology; vol. 400).

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

Helicobacter pylori CagL Hypervariable Motif: A Global Analysis of Geographical Diversity and Association With Gastric Cancer

Gorrell, R. J., Zwickel, N., Reynolds, J., Bulach, D. M. & Kwok, T., 2016, In : Journal of Infectious Diseases. 213, 12, p. 1927-1931 5 p.

Research output: Contribution to journalArticleResearchpeer-review

The three-dimensional structure of the extracellular adhesion domain of the sialic acid-binding adhesin SabA from Helicobacter pylori

Pang, S. S., Nguyen, T. S., Perry, A. J., Day, C. J., Panjikar, S., Tiralongo, J., Whisstock, J. & Kwok, T., 2014, In : Journal of Biological Chemistry. 289, 10, p. 6332 - 6340 9 p.

Research output: Contribution to journalArticleResearchpeer-review

A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system

Gorrell, R. J., Guan, J. S., Xin, Y., Anoushiravani Tafreshi, M., Hutton, M. L., McGuckin, M. A., Ferrero, R. L. & Kwok, T., 2013, In : Cellular Microbiology. 15, 4, p. 554 - 570 17 p.

Research output: Contribution to journalArticleResearchpeer-review

Helicobacter pylori type IV secretion system and its adhesin subunit, CagL, mediate potent inflammatory responses in primary human endothelial cells

Tafreshi, M., Guan, J., Gorrell, R. J., Chew, N., Xin, V., Deswaerte, V., Rohde, M., Daly, R. J., Peek Jr, R. M., Jenkins, B. J., Davies, E. M. & Kwok, T., 6 Feb 2018, In : Frontiers in Cellular and Infection Microbiology. 8, FEB, 15 p., 22.

Research output: Contribution to journalArticleResearchpeer-review

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